The mechanism of regulation of the human anti-influenza response will be analyzed in vitro, with a sensitive assay for inducing and assaying anti-influenza antibody, and T cell clones of various types - helper, suppressor inducer and suppressor effector. Regulation of the influenza response and of T cell clones will be analyzed in several ways, e.g. Immunological Tolerance, using high concentrations of antigen (purified influenza proteins and peptides. We will try to induce tolerance in helper cell clones, and will test whether suppressor cells (SC) are needed for tolerance induction. If tolerance is induced (with suppressor cells or not), we will test mechanisms of T cell tolerance directly, e.g. cell death, receptor blockade, or lack of receptor regeneration. Antibody suppression will be analyzed both on T cell clones and antibody responses. We will induce suppressor cells using high concentrations of purified proteins, or peptides in the absence of presenting cells and maintain the purified OKT8+ cells with suppressor inducer factors, or feeder cells, or TCGF, to yield suppressor cell clones. Anti-idiotype regulation of T cells, by T cells, will be investigated by generating clones against our existing helper clones, and determining whether these are suppressor, or killer cells; and by analyzing their effects on helper clones. This will provide a strategy for influencing disease processes which involve aberrant T cell function e.g. autoimmunity. By understanding immune regulation of a well defined human response system for both T and B cells we can begin to understand human immune regulation, and its disorders.